Lipoic acid plays a vital role in aerobic energy metabolism in mammals, plants, and bacteria. Despite its metabolic importance the enzymes responsible for the synthesis and covalent attachment of this enzyme cofactor remain poorly understood. A number of recent advances in our knowledge of these processes has occurred in bacterial systems. Given these data and the fact that mitochondria are derived from endosymbiotic bacteria, it seems likely that the bacterial pathways are conserved in mammalian mitochondria, the cellular compartment where the lipoic acid-modified proteins reside. This proposal is to examine mammalian mitochondrial lipoic acid metabolism and test if the proteins involved function as do those in bacteria.